A scalable outpatient framework for BI-RADS 2-4B breast nodule management: an iodine-DMSO transdermal protocol.

BACKGROUND: Low- to intermediate-suspicion breast nodules (BI-RADS 2-4B) generate diagnostic uncertainty, prolonged surveillance, and emotional and operational burden, often without established low-risk interventions designed to support short-interval physiological modulation. Given the redox, endocrine, vascular, and microenvironmental dependencies of benign breast lesions, physiology-guided outpatient modulation may contribute to response-oriented decision-making before conventional oncologic escalation. METHODS: A structured translational outpatient protocol was developed through mechanistic evidence synthesis, multicriteria translational prioritization, protocol structuring, and exploratory clinical implementation. The workflow integrated Evidence-Informed Design, Work Breakdown Structure, multicriteria decision analysis (MCDA), and DesignThinking/Open Innovation. Systematic reviews of molecular iodine and dimethyl sulfoxide (DMSO) identified translational response domains and mechanistic convergence pathways associated with tissue accessibility, redox modulation, and outpatient feasibility. RESULTS: The translational synthesis identified redox modulation, vascular responsiveness, microenvironmental stabilization, tissue accessibility, and immune-related physiological modulation as principal mechanistic domains associated with iodine-responsive breast-tissue modulation. Comparative prioritization identified the transdermal route as the most operationally feasible outpatient configuration. The finalized protocol-2.5 mL of Lugol's solution (5% iodine) combined with 2.5 mL of pharmaceutical-grade DMSO (99.9%), applied transdermally twice weekly for five weeks-was implemented in three exploratory BI-RADS 4B cases using short-interval MRI and ultrasound reassessment. Two cases demonstrated complete radiologic resolution accompanied by vascular-signal normalization and stromal remodeling, including simultaneous remodeling of contralateral BI-RADS 2 nodules; one remained lesion-free during 12-month follow-up. A third case demonstrated a partial imaging-response pattern and was referred for fine-needle aspiration according to predefined reassessment criteria. No major adverse effects or tolerability-related discontinuations occurred; the intervention was discontinued after six sessions in the third case according to the predefined imaging-based stopping rule. DISCUSSION: The framework integrates physiological modulation with response-oriented imaging reassessment while preserving compatibility with conventional oncologic workflows. Its low-complexity and reproducible outpatient architecture may possess translational relevance within resource-sensitive and Value-Based Healthcare-oriented breast-care settings. CONCLUSIONS: The exploratory implementation of the iodine-DMSO transdermal protocol yielded biologically coherent, imaging-detectable, and operationally reproducible response patterns compatible with short-interval physiological modulation. These findings support controlled outpatient and implementation-oriented investigations evaluating reproducibility, scalability, cost impact, and broader translational applicability. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251122511, PROSPERO CRD420251122511; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251123805, PROSPERO CRD420251123805.